We have found that prolonged stimulation results in an increase in the size of the quanta at the frog neuromuscular junction. Preliminary evidence suggests that the increase is due to more acetylcholine in each quantum, rather than to an increased sensitivity of the end-plate to the transmitter. We have also found that including certain lectins or anions in the bathing solution during stimulation results in still larger quantal size. We will now investigate in detail the mechanism by which quantal size is altered, using both electrophysiological and morphological techniques. The preliminary physiological evidence suggests that the size of the synaptic vesicles will be increased by the treatments. The idea that quantal size is a variable that depends on the past treatment of the junction is novel, and has many implications for the functioning of nervous systems. An understanding of the mechanism by which the lectins or anions change quantal size may lead to the development of therapeutic methods for altering quantal size, which would be extremely useful in the treatment of neuromuscular disease. We will also investigate the possibility of interactions in quantal release by nerve stimulation at the neuromuscular junction. There is some evidence that the release of one quantum changes the probability of the release of additional quanta. We are studying this process by observing releases from a small length of the nerve terminal, by working in calcium-free Ringer and exposing only a short length of the terminal to calcium released from a micropipette. The elucidation of the interactions in quantal release will be important for our understanding of the operation of synapses.